| Project/Area Number |
14370264
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kurume University School of Medicine |
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Principal Investigator |
HASHIMOTO Takashi Kurume University School of Medicine, Professor, 医学部, 教授 (20129597)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMOTO Shinichiro Kurume University School of Medicine, Associate Professor (10220162)
KUSUHARA Masahiro Kurume University School of Medicine, Assistant Professor (40195441)
KARASHIMA Tadashi Kurume University School of Medicine, Assistant Professor (70211175)
森 理 久留米大学, 医学部, 助教授 (10175630)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | desmosome / autoimmune / mutation / plakophilin / desmocollin / envoplakin / periplakin / desmoyokin / 表皮 / 天疱瘡 / デスモグレイン / 自己抗体 / 遺伝子 / 遺伝子検索 / エンポプラキン |
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| Research Abstract |
By immunofluorescence using COS-7 cells transfected with cDNAs of human desmocollins 1-3, we have shown that some pemphigus sera contained IgA antibodies reactive with desmocollins. There are two subtypes of IgA pemphigus, IEN type and SPD type. By immuno-electron microscopic study, we have shown that IgA antibodies of SPD type IgA pemphigus reacted with desmosomal areas, whereas IgA antibodies of IEN type IgA pemphigus reacted with non-desmosomal areas. We have shown that most of the sera of IgG/IgA pemphigus had IgG and IgA antibodies reactive with Dsg1/Dsg3 and Dsc1. In addition, by immuno-electron microscopic study, it is shown that these sera reacted with desmosomal areas. We have examined a large family with patients showing acantholytic blister above the basal layer. First, we examined desmoglein 3 gene, but we could not find a mutation. However, we have found a mutation in the ATP2A2 gene, encoding SERCA2, the causative gene of Darier disease. In a patient showing superficial blister formation in the epidermis, we have not detected any mutations in the genes of desmosomal proteins. In stead, in this patient, we have found a mutation in the C-terminal area of keratin 1 gene. We have produced various recombinant proteins of envoplakin and periplakin. By immunoblotting using theses recombinant proteins, we have shown that most paraneoplastic pemphigus patients reacted with various domains of envoplakin and periplakin. We have succeeded to produce knockout mice of desmoyokin. We could not find any morphological abnormality in the desmosomes. In addition,. the cell culture from the knockout mice did not show an abnormal cell adhesion.
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